These investigations are intended to increase our understanding of the population biology of bacteria, their viruses and plasmids and the mechanisms of evolution at the molecular level. The studies of the population biology of bacteria are being performed at both a theoretical and experimental level. Mathematical models of resource limited population growth and competition, and for the interactions of bacteria and their viruses and plasmids have been developed. In the analysis of their properties primary concern is given to the necessary and sufficient conditions for stable regimes of co- existence for competing bacterial species and for bacteria with their virulent viruses and conjugally transmitted plasmids. To test the reality of this theory, experiments are performed with chemostat and serial transfer populations of Escherichia coli and T phage and F', R, and colicin plasmids. An experimental examination is made of the relationship between protein variation and selection, and the rates of base substitution mutation in E. coli. Two proteins of known in vivo function are being studied, B-galactosidase and alkaline phosphatase. Functional variants of the lacz and pho loci are obtained by selecting revertants from lacz - and pho- mutants and from surveys of natural populations of E. coli. The primary concern of these investigations is the association between the catalytic efficiency of enzymes and allelic fitness. Base substitution mutation rates are estimated by determining the intracistronic reversion frequencies from chain terminating nonsense mutants.